Theory, analysis, and interpretation of single-molecule force spectroscopy experiments
Theory, analysis, and interpretation of single-molecule force spectroscopy experiments
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DOI：
10.1073/pnas.0806085105
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发表时间：
2008-10-14
影响因子：
11.1
通讯作者：
Szabo, Attila
中科院分区：
文献类型：
--
作者：
Dudko, Olga K.;Hummer, Gerhard;Szabo, Attila
动态力光谱探测单分子和分子组装体的动力学和热力学性质。在这里，我们提出了一个简单的程序，从这样的实验中提取动力学信息。我们的方法的基石是在不同的力加载速率下获得的断裂力直方图转化为在恒定力实验中可测量的力相关寿命。为了解释力依赖的寿命，我们推导出一个概括的贝尔公式，是正式的Kramers理论的框架内准确。这一结果补充了分析表达式的寿命，我们以前推导出的一类模型潜力。我们通过分析DNA发夹的纳米孔解压缩和通过柔性连接器连接到原子力显微镜的蛋白质的展开来说明我们的过程。我们的程序，将断裂力直方图的力依赖的寿命仍然有效，即使当分子的延伸是一个穷人的反应坐标和高维自由能表面必须考虑。在这种情况下，寿命的微观解释变得更具挑战性，因为寿命可以揭示更丰富的，甚至是非单调的，对力的依赖。
Dynamic force spectroscopy probes the kinetic and thermodynamic properties of single molecules and molecular assemblies. Here, we propose a simple procedure to extract kinetic information from such experiments. The cornerstone of our method is a transformation of the rupture-force histograms obtained at different force-loading rates into the force-dependent lifetimes measurable in constant-force experiments. To interpret the force-dependent lifetimes, we derive a generalization of Bell's formula that is formally exact within the framework of Kramers theory. This result complements the analytical expression for the lifetime that we derived previously for a class of model potentials. We illustrate our procedure by analyzing the nanopore unzipping of DNA hairpins and the unfolding of a protein attached by flexible linkers to an atomic force microscope. Our procedure to transform rupture-force histograms into the force-dependent lifetimes remains valid even when the molecular extension is a poor reaction coordinate and higher-dimensional free-energy surfaces must be considered. In this case the microscopic interpretation of the lifetimes becomes more challenging because the lifetimes can reveal richer, and even nonmonotonic, dependence on the force.